Nucleic acids are the fundamental informational molecules of all living organisms. We propose to explore the three-dimensional structural details of the interactions of nucleic acids with themselves and other biologically important molecules by means of single crystal x-ray crystallography. We wish to explore the non-covalent sequence specific recognition of nucleic acids by drug, peptides, cations, water and other probes. The primary path by which these phenomena will be studied will be by crystallization of short, defines-sequence fragments of double helical nucleic acids complexed both with cations and drugs which bind to them in a sequence specific fashion. We believe that these studies will provide much hard geometric data about the intimate conformational and configurational details of the sequence specific recognition of nucleic acids. Via this data, we hope to gain insight into the molecular basis of the mode of drug action and the mechanism of gene expression.